Substances present on the membranes of fetal cells serve as "autoantigens" in inbred rodents. Cytotoxic effector cells from pregnant animals or animals immunized with fetal cells destroy a large spectrum of tumor cells which possess comparable antigens. Human cancers have cross-reacting antigens and mounting evidence suggests that these may be of fetal origin. The precise cut-off point in the expression of fetal antigen in the membrane of developing fetal cells cross-reactive with several tumor lines was the elventh day of gestation in the hamster and the sixteenth day in the mouse. Term fetus and adult cells do not overtly display these antigens. Gross biochemical changes in the membrane have been detected coordinate with silencing or masking of the fetal antigen. This proposal requests support to examine fetal antigen expression in the hamster and mouse as these antigens relate immunologically to tumors induced by viruses and chemicals. A major objective will be to correlate, immunochemically, tumor specific transplantation antigens (TSTA) with fetal antigens on tumors and in fetus. For this purpose, cell-free antigens have been developed and these will be examined by several semi-quantitative immunologic procedures involving antibody and cell-mediated immune reactions to determine the relationship of fetal antigens to TSTA and other tissue antigens (Forssman, organ and blood-group specific antigen, isoantigens). A unique opportunity exists to investigate fetal antigens biochemically and structurally and correlate their presence to the immune responses produced by the host to tumors possessing fetal antigens so that the significance of these antigens in neoplasia can be understood.